Can bleeding occur in postmenopausal women on Hormone Replacement Therapy (HRT)?

From the Guidelines

Yes, bleeding can occur in postmenopausal women on Hormone Replacement Therapy (HRT). This is a common side effect, especially during the first 3-6 months of treatment. For women on cyclic HRT (estrogen plus progestogen taken sequentially), scheduled withdrawal bleeding is expected. For those on continuous combined HRT (estrogen and progestogen taken daily), irregular spotting or bleeding may occur initially but should diminish over time. If bleeding persists beyond 6 months on continuous HRT, becomes heavy, or occurs after a period of no bleeding, it requires prompt medical evaluation to rule out endometrial hyperplasia or cancer. The bleeding occurs because HRT stimulates the endometrial lining, and when progestogen is withdrawn or if the endometrium breaks down irregularly, bleeding results. Women should track any bleeding patterns and report them to their healthcare provider, who may recommend an endometrial biopsy, ultrasound, or other investigations if the bleeding pattern is concerning 1.

Key Points to Consider

• The risk of bleeding is higher in the first few months of HRT treatment.
• Women on cyclic HRT can expect scheduled withdrawal bleeding.
• Women on continuous combined HRT may experience irregular spotting or bleeding that should diminish over time.
• Persistent, heavy, or unexpected bleeding requires medical evaluation to rule out endometrial hyperplasia or cancer.
• HRT stimulates the endometrial lining, which can lead to bleeding when progestogen is withdrawn or the endometrium breaks down irregularly.

Recommendations for Healthcare Providers

• Educate women on the potential for bleeding as a side effect of HRT.
• Instruct women to track their bleeding patterns and report any concerns to their healthcare provider.
• Perform prompt medical evaluation for women experiencing persistent, heavy, or unexpected bleeding.
• Consider endometrial biopsy, ultrasound, or other investigations if the bleeding pattern is concerning.

From the FDA Drug Label

Adequate diagnostic measures, such as directed or random endometrial sampling, when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding.

Bleeding can occur in postmenopausal women on Hormone Replacement Therapy (HRT). The FDA drug label recommends that adequate diagnostic measures be taken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding 2.

• Key points:
  • Abnormal genital bleeding is a potential side effect of HRT.
  • Diagnostic measures should be taken to rule out malignancy.
  • The risk of endometrial cancer is increased with the use of unopposed estrogen therapy in women with a uterus.
  • Adding a progestin to postmenopausal estrogen therapy can reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer 2.
  • Women taking HRT should be monitored regularly for signs of bleeding or other side effects 2.

From the Research

Bleeding on HRT in Postmenopausal Women

• Bleeding can occur in postmenopausal women on Hormone Replacement Therapy (HRT) 3, 4, 5, 6, 7.
• The frequency and duration of bleeding vary depending on the type and dose of HRT regimen used 3, 5, 7.
• Continuous combined HRT regimens tend to have a better bleeding profile than other types of HRT regimens 4, 7.

Factors Influencing Bleeding on HRT

• Endometrial thickness at the start of treatment can predict the chance of achieving amenorrhea during early HRT 3.
• Body mass index, age, and blood pressure have no predictive value for bleeding problems 3.
• Initial gestagen treatment may decrease the frequency of breakthrough bleeding during continuous combined HRT 6.

Comparison of HRT Regimens

• Oral HRT regimens tend to have a better bleeding profile than transdermal formulations 7.
• The E2/P4 combination is amongst those with lower bleeding rates and may be an appropriate alternative for women seeking bioidentical HRT and/or those who have bleeding concerns with other HRT 7.
• Different HRT regimens have varying rates of amenorrhea, with cumulative amenorrhea over a year ranging from 18 to 61% 7.